JPH11279067A - Bufonis venenum-formulated internal liquid preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject liquid preparation obtainable by a simple producing method, stabilized in bufosteroid which is a main pharmacentical effect ingredient of Bufonis venenum and capable of keeping desired pharmacentical action of Bufonis venenum by adjusting the pH in a specific range. SOLUTION: This internal liquid preparation is prepared in the range of pH 4.0-7.0. A buffer agent such as Soerensen (sodium citrate and sodium hydroxide) is preferably used in order to control the pH. The liquid preparation is obtained by dissolving, e.g. Bufonis venenum in a hydroxylic solvent such as propylene glycol, adding an antiseptic agent thereto, separately adding a sweetener, a buffer agent, etc., to purified water and as necessary, adding other crude medicine extract, etc., thereto, adding Bufonis venenum-containing solution previously dissolved to the aqueous solution, filtering the solution, packing the solution into a bottle, as necessary, sterilizing the contents.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an oral liquid preparation containing senso, which stabilizes bufosteroids, which are the main medicinal components of senso.

[0002]

2. Description of the Related Art Many pharmacological actions of senso have been reported for senso, such as inotropic, local anesthesia, anti-inflammation, muscle relaxation, blood pressure lowering, and suppression of gastric juice secretion, and are listed in the Japanese Pharmacopoeia. It is a useful crude drug. Senso is a processed and dried white serum secreted from the posterior glands and skin glands of the toad or its relatives, and has been used for inoculation, analgesia, antiphlogistic and detoxification since ancient times. Senso's name was first seen in "Honzo Engi" published in the Song Dynasty in China,
Chinese toad or its close relatives, which is the protozoan of Senso, is listed as a toad in China's oldest herbal book, Shinnohon Honkyo, and has a very long history as a drug.

However, since Senso has a strong irritating bitterness and a strong local anesthetic effect, it can give a persistent numbness by keeping it in the mouth for a short period of time. It was difficult to develop a liquid formulation. Senso has been urgently desired to be formulated as a liquid preparation in view of its efficacy, but it has been strongly desired from the viewpoint of its rapid effect, but components such as bufalin, cinobfagin, and rejibufogenin, which play a central role in the pharmacology of senso, are known. Since bufosteroids are extremely unstable in an aqueous solution, it has been difficult to formulate a stable and easy-to-take Senso-containing internal liquid preparation.

The problem of stabilization of bufosteroid in an aqueous solution has been improved by preparing an inclusion compound with bufosteroid using cyclopolyglucan (Japanese Patent Application Laid-Open No. 50-160416). In addition, a method of improving the problem relating to bitterness of senso by adding cyclodextrin has been considered (Japanese Patent Application Laid-Open No. 61-233624).

[0005]

However, the method for producing an inclusion compound with bufosteroids using cyclopolyglucan requires a long time for the production because the production method is complicated, and the method for producing bufosteroids is complicated. Since the clathrate compound is a compound different from the original bufosteroids, it is possible to maintain the desired pharmacological action of senso, which has bufosteroids as the main active ingredient, which has been confirmed by experiments. It may not be possible. In addition, the method of improving bitterness by adding cyclodextrin is also considered to include an inclusion compound of bufosteroids, similar to the case of using cyclopolyglucan. May not be able to maintain.

Accordingly, an object of the present invention is to provide an oral liquid preparation which is simple in its production method, stabilizes bufosteroids which are the main medicinal components of senso, and maintains the desired pharmacological action of senso. I do.

[0007]

SUMMARY OF THE INVENTION The present invention has been made to achieve the above object, and has a pH of from 4.0 to 7.0.
This is a senso-containing oral solution prepared in the range of 0. Thus, by preparing a senso-containing oral solution at a pH in the range of 4.0 to 7.0, bufosteroids can be used as the main active ingredient of senso without changing to other compounds such as clathrates. Since certain bfosteroids can be stabilized, the desired pharmacological action of senso can be maintained. Further, by adjusting the pH, the stabilization of the bufosteroids can be achieved, so that the production thereof is simple. The method for producing a Senso-containing oral liquid preparation of the present invention is characterized in that the pH is adjusted within a range of 4.0 to 7.0.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The oral solution containing senso according to the present invention has a pH in the range of 4.0 to 7.0, preferably 5.
It is prepared within the range of 0 to 6.0. By adjusting the pH to 4.0 to 7.0, preferably 5.0 to 6.0, it is possible to stabilize bufosteroids, which are the main active ingredients of Senso.

In the present invention, as a buffer for adjusting the pH, Clark-Lubs (potassium hydrogen phthalate, sodium hydroxide), Sφrensen (sodium citrate, sodium hydroxide), Michaelis
(Acetic acid, sodium acetate), Mcllvain (sodium hydrogen phosphate, citric acid) and the like, but sodium citrate, a citric acid buffer and the like can be used.

[0010] The present invention is applied to a drug containing Senso. For pharmaceuticals, for example, drug manufacturing guidelines
(1997 edition), there are cardiotonic drugs Rokjin-maru and other preparations containing Senso. The crude drugs used in the formulation together with Senso include musk, cow yellow, ginseng, animal gall, tiger goat, agarwood, dragon brain, saffron, deer mushrooms, asenyaku, rhododendron, pearls, oren, and epimedium. In other senso-containing preparations, thiamine nitrate, ascorbic acid, aminoethylsulfonic acid, DL-methionine, ferrous fumarate, and the like can be added in addition to the crude drug.

The crude drugs used in the preparation of the present invention include:
Powder, extract, extract powder, etc. Further, as an additive used when manufacturing the preparation according to the present invention, for example, pH
Buffering agents, surfactants, propylene glycol, glycerin, polyethylene glycol and the like as hydroxylic solvents, sucrose and D-sorbitol as sweeteners, methyl paraoxybenzoate, butyl paraoxybenzoate, sodium benzoate and the like as preservatives In addition, coloring agents, fragrances, and the like can be added as needed.

As the surfactant, polyoxyethylene hydrogenated castor oil (trade name: HCO Nikko Chemicals), sucrose fatty acid ester (trade name: DK ester F-)
160 and F-140, Daiichi Kogyo Seiyaku Co., Ltd.), polyglycerin fatty acid ester (trade name: decaglyceryl monostearate and decaglyceryl monolinoleate, Nikko Chemicals), polyoxyethylene sorbitan higher fatty acid ester (trade name: Tween)・ Atlas).

[0013] The method for producing an oral liquid preparation according to the present invention includes:
There are the following: For example, after dissolving senso in a hydroxylic solvent such as propylene glycol, add a preservative, separately add a sweetener and a buffer to purified water, heat and dissolve, add a surfactant, and if necessary, add a surfactant. If other crude drug extracts are added. The senso-containing solution previously dissolved is added to this aqueous solution to make it uniform. Next, this solution is filtered, filled into a bottle, sterilized if necessary, and then manufactured as an internal liquid solution.

[0014]

Next, an embodiment of the present invention will be described.
The present invention is not limited to these examples. First
The Senso-compounded oral liquid according to the example is Senso powder 10m.
g was added to 10 mL of propylene glycol, dispersed and dissolved, and the citrate buffer having a pH of 3, 4 was added thereto.
5.5, 6, 7, and 8 phosphate buffers and purified water were added to 300 mL. After the solution was filtered through a glass filter and then a membrane filter, 30 mL of a transparent glass vial was filled in 30 mL portions, and the solution was capped with a rubber stopper and an aluminum cap.

[0015] The oral liquid formulation containing senso according to the second embodiment is
By using the components shown in Table 1 and by the same manufacturing method as in the first example, oral liquids of pH 4, 5 and 6, respectively, were prepared.

[0016]

[Table 1]

The solution prepared in Example 1 was heated at 70.degree.
The liquid preparation prepared in Example 2 was stored in a thermostat at 40 ° C. for 3 months for 4 days, and the content of bufosteroids in the senso component was measured. Tables 2 and 3 show the results. From Tables 2 and 3, it was found that by adjusting the pH of the Senso-containing oral solution within the range of 4.0 to 7.0, the main active ingredient bufosteroids can be stabilized.

[0018]

[Table 2]

[0019]

[Table 3]

[0020]

As described above, according to the present invention, an oral liquid preparation which is simple in its production method, stabilizes bufosteroids, which is the main medicinal component of senso, and maintains the desired pharmacological action of senso Can be provided.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Shoji Higashima, Inventor Shoichi Pharmaceutical Co., Ltd. 1-27-1 Wada, Suginami-ku, Tokyo (72) Keiichi Sudo Inventor Keiichi Sudo 1-27-17, Wada, Suginami-ku, Tokyo (72) Inventor Kenji Oda 1-21-7, Wada, Suginami-ku, Tokyo Inventor Kenji Oda

Claims (1)

[Claims] 1. A senso-containing oral solution prepared at a pH in the range of 4.0 to 7.0.